1. Field of the Invention
The invention relates to compounds, compositions and methods for inhibiting (preventing and treating) neovascularization (angiogenesis).
2. Prior Work
Malignant neovascularization (angiogenesis), particularly ocular neovascularization associated with macular degeneration, diabetic retinopathy and retinopathy of prematurity, as well as psoriasis, rheumatoid arthritis and solid tumors, is a serious medical condition.
The most common cause of blindness in Americans over age 55 is age-related macular degeneration (AMD); for those under 40, diabetes is the most common cause of blindness. Neovascularization is the root cause of blindness in both cases. Neovascularization is the result of a compromise of the vascular bed supplying the retina, and may be regarded as a response to tissue ischemia (or hypoxia). Clinicians have long recognized the high probability of neovascularization in individuals who have lost part of the capillary bed due to diabetes, or who have experienced occlusion of a branch vein of the retina.
The primary current treatment for neovascularization is destructive. Photocoagulation is used to reduce the volume of hypoxic tissue in diabetic retinopathy or to destroy vessels in AMD. Cryotherapy may be used to destroy hypoxic retina in infants. There is an urgent need for therapeutic intervention in these disease processes. No known therapeutic treatment can prevent neovascularization following loss of capillaries in diabetes, reduce the risk of further neovascularization in wet AMD, or offer reassurance to patients at risk because of heredity, diabetes, or age.
Any progress toward therapeutic management and prevention of neovascularization will greatly reduce the social and economic impact of diabetes and AMD.
One of the limitations of the newer therapeutic approaches to neovascularization that are under development, particularly those involving growth factors, is that they may also inhibit wound repair or the development of collateral vessels in mild occlusion of coronary arteries.